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healthy controls. CSF levels of amyloid \u03b2 (A\u03b2)1\u201042, A\u03b21\u201040, A\u03b21\u201038, and soluble \u03b2 fragment of APP (sAPP\u03b2) were centrally analyzed. We compared CSF levels of APP\u2010derived peptides between groups and, we studied the correlation between CSF biomarkers, cortical thickness, and domain\u2010specific cognitive composites in each group. Then, we explored the relationship between cortical thickness, CSF levels of APP\u2010derived peptides, and regional gene expression profile using a brain\u2010wide regional gene expression data in combination with gene set enrichment analysis.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>The CSF levels of A\u03b21\u201040, A\u03b21\u201038, and sAPP\u03b2 were lower in the FTLD\u2010related syndromes group than in the AD and healthy controls group. CSF levels of all APP\u2010derived peptides showed a positive correlation with cortical thickness and the executive cognitive composite in the FTLD\u2010related syndromes group but not in the healthy control or AD groups. In the cortical regions where we observed a significant association between cortical thickness and CSF levels of APP\u2010derived peptides, we found a reduced expression of genes related to synaptic function.<\/jats:p><\/jats:sec><jats:sec><jats:title>Interpretation<\/jats:title><jats:p>APP\u2010derived peptides in CSF may reflect FTLD\u2010related neurodegeneration. This observation has important implications as A\u03b21\u201042 levels are considered an indirect biomarker of cerebral amyloidosis.<\/jats:p><\/jats:sec>","DOI":"10.1002\/acn3.50948","type":"journal-article","created":{"date-parts":[[2019,12,2]],"date-time":"2019-12-02T23:12:10Z","timestamp":1575328330000},"page":"2518-2530","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":18,"title":["APP\u2010derived peptides reflect neurodegeneration in frontotemporal dementia"],"prefix":"10.1002","volume":"6","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-5418-2052","authenticated-orcid":false,"given":"Ignacio","family":"Ill\u00e1n\u2010Gala","sequence":"first","affiliation":[{"name":"Memory Unit Department of Neurology Hospital de la Santa Creu i Sant Pau Biomedical Research Institute Sant Pau Universitat Aut\u00f2noma de Barcelona Barcelona Spain"},{"name":"Centro de Investigaci\u00f3n Biom\u00e9dica en Red de Enfermedades 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